The Clinical Implications of Tumor Mutational Burden in Osteosarcoma.
osteosarcoma
overall survival
progression-free survival
tumor mutational burden
whole-exome sequencing
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
16
08
2020
accepted:
10
12
2020
entrez:
26
4
2021
pubmed:
27
4
2021
medline:
27
4
2021
Statut:
epublish
Résumé
Osteosarcoma (OTS) is aggressive bone malignancy without well-recognized prognosis biomarker. Tumor mutational burden (TMB) has been proved as effective biomarker in predicting clinical outcomes in several cancer types. However, its prognostic value in OTS remains unknown. In this study, we aim to evaluate the implication of TMB in OTS patients. To depict the landscape of somatic mutations in OTS, we performed Whole-Exome Sequencing (WES) on 31 OTS tissue samples and corresponding White Blood Cells (WBCs) as matched control. TMB was calculated as the total number of somatic alterations in coding regions normalized to the per sequenced genomic megabase (~30.4Mb in WES). The prognostic values of TMB were evaluated by Kaplan-Meier methods and Cox regression models. The median age was 16.0 years at diagnosis, and 54.8% of patients were male. The most common genetic alterations were mainly involved in cell cycle and DNA damage response and repair, including H3F3A, TP53, MYC, and CDKN2A/B. The median progression-free survival (PFS) was 775.5 days in TMB-High (defined as third quartile of TMB value, <2.565) versus 351 days in TMB-Low (<2.565). All patients with TMB-High are PFS-Long (>400 days), while 36.4% of all patients with TMB-Low were PFS-Long ( TMB-High can be used as prognostic marker for OTS. Our findings demonstrate that TMB may be helpful in combination with traditionally clinicopathologic risk factors to optimize risk stratification and guide treatment decisions.
Sections du résumé
BACKGROUND
BACKGROUND
Osteosarcoma (OTS) is aggressive bone malignancy without well-recognized prognosis biomarker. Tumor mutational burden (TMB) has been proved as effective biomarker in predicting clinical outcomes in several cancer types. However, its prognostic value in OTS remains unknown. In this study, we aim to evaluate the implication of TMB in OTS patients.
METHODS
METHODS
To depict the landscape of somatic mutations in OTS, we performed Whole-Exome Sequencing (WES) on 31 OTS tissue samples and corresponding White Blood Cells (WBCs) as matched control. TMB was calculated as the total number of somatic alterations in coding regions normalized to the per sequenced genomic megabase (~30.4Mb in WES). The prognostic values of TMB were evaluated by Kaplan-Meier methods and Cox regression models.
RESULTS
RESULTS
The median age was 16.0 years at diagnosis, and 54.8% of patients were male. The most common genetic alterations were mainly involved in cell cycle and DNA damage response and repair, including H3F3A, TP53, MYC, and CDKN2A/B. The median progression-free survival (PFS) was 775.5 days in TMB-High (defined as third quartile of TMB value, <2.565) versus 351 days in TMB-Low (<2.565). All patients with TMB-High are PFS-Long (>400 days), while 36.4% of all patients with TMB-Low were PFS-Long (
CONCLUSIONS
CONCLUSIONS
TMB-High can be used as prognostic marker for OTS. Our findings demonstrate that TMB may be helpful in combination with traditionally clinicopathologic risk factors to optimize risk stratification and guide treatment decisions.
Identifiants
pubmed: 33898301
doi: 10.3389/fonc.2020.595527
pmc: PMC8059407
doi:
Types de publication
Journal Article
Langues
eng
Pagination
595527Informations de copyright
Copyright © 2021 Xie, Yang, Guo, Che, Xu, Sun, Liu, Ren, Liu, Yang, Ji and Tang.
Déclaration de conflit d'intérêts
YFY and DC are the employees of Genetron Health (Beijing) Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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